Premium
Simvastatin Does Not Affect CYP3A Activity, Quantified by the Erythromycin Breath Test and Oral Midazolam Pharmacokinetics, in Healthy Male Subjects
Author(s) -
Prueksaritat Thomayant,
Vega José M.,
Rogers J. Douglas,
Gagliano Kathleen,
Greenberg Howard E.,
Gillen Lisa,
Brucker Mary Jo,
McLoughlin Debra,
Wong Peggy H.,
Waldman Scott A.
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/009127000004001112
Subject(s) - simvastatin , midazolam , pharmacokinetics , cyp3a , pharmacology , medicine , erythromycin , oral administration , dosing , cmax , drug interaction , cyp3a4 , pharmacodynamics , chemistry , antibiotics , cytochrome p450 , biochemistry , metabolism , sedation
Potential for inhibition of CYP3A activity by simvastatin, an HMG‐CoA reductase inhibitor, was evaluated in 12 healthy male subjects who received placebo or 80 mg of simvastatin, the maximal recommended dose, once daily for 7 consecutive days. On day 7, an intravenous injection of 3 μCi [ 14 C N‐methyl]erythromycin for the erythromycin breath test (EBT) was coadministered with a 2 mg oral solution of midazolam. The values for percent 14 C exhaled during the first hour (for EBT) and the pharmacokinetic parameters of midazolam (AUC, C max , t 1/2 ) were not affected following multiple once‐daily oral doses of simvastatin 80 mg. The 95% confidence interval was 0.97 to 1.18 for EBT and 0.99 to 1.23 for midazolam AUC. In addition, the total urinary recoveries of midazolam and its 1′‐hydroxy metabolites (free plus conjugate) obtained from both treatments were not statistically different ( p > 0.200). These data demonstrate that multiple dosing of simvastatin, at the highest recommended clinical dose, does not significantly alter the in vivo hepatic or intestinal CYP3A4/5 activity as measured by the commonly used EBT and oral midazolam probes .